The invention relates to a process for preparing carboxylic acid esters. Carboxylic acid esters can be used, for example, as solvents. They are also intermediates in chemical synthesis.
U.S. Pat. No. 5,405,991 discloses the preparation of esters of trifluoroacetic acid and of chlorodifluoroacetic acid from the acid chlorides and the corresponding alcohol in the presence of xe2x80x9coniumxe2x80x9d salts of the carboxylic acid corresponding to the carboxylic acid chloride used.
Published German patent application no. DE 197 32 031 discloses the preparation of esters of trifluoroacetic acid and of chlorodifluoroacetic acid in the presence of the corresponding xe2x80x9coniumxe2x80x9d salts with 2-phase formation for the purpose of simple separation of the products.
It is an object of the present invention to devise an improved process for the preparation of carboxylic acid esters from alcohols and carboxylic acids, carboxylic acid chlorides or carboxylic acid bromides.
These and other objects are achieved in accordance with the present invention by providing a process for preparing a carboxylic acid ester from an alcohol and a carboxylic acid, carboxylic acid chloride or carboxylic acid bromide, wherein esterification is effected while avoiding precipitation of xe2x80x9coniumxe2x80x9d salts, by operating in the presence of an onium salt adduct of the corresponding carboxylic acid and 1,5-diazabicyclo[4.3.0]-non-2-ene or 1,8-diazabicyclo[5.4.0]-undec-7-ene, or operating in the presence of the corresponding carboxylic acid and an onium salt of the corresponding carboxylic acid.
The process according to the invention for the preparation of carboxylic acid esters from alcohols and carboxylic acids, carboxylic acid chlorides or carboxylic acid bromides provides for the esterification to be performed, avoiding the precipitation of xe2x80x9coniumxe2x80x9d salts, by
operating in the presence of the adduct (xe2x80x9coniumxe2x80x9d salt) of the corresponding carboxylic acid and 1,5-diazabicyclo[4.3.0]-non-5-ene (xe2x80x9cDBNxe2x80x9d) or 1,8-diazabicyclo[5.4.0]-undec-7-ene (xe2x80x9cDBUxe2x80x9d), or
operating in the presence of the corresponding carboxylic acid and an xe2x80x9coniumxe2x80x9d salt of the corresponding carboxylic acid.
Preferably the starting materials in the preparation of carboxylic acid esters according to the invention are alcohols and carboxylic acid chlorides. The advantage of the process of the invention is that the precipitation of solids (primarily hydrohalide salts of the xe2x80x9coniumxe2x80x9d cations) is prevented. Precipitated solids are undesirable in the reaction and working-up of the reaction mixture. The term xe2x80x9calcoholsxe2x80x9d also includes thioalcohols. The terms xe2x80x9ccarboxylic acids, carboxylic acid chlorides or carboxylic acid bromidesxe2x80x9d also cover the corresponding thiocarboxylic acids or thiocarboxylic acid derivatives.
The process will be explained in further detail with reference to illustrative representative embodiments using carboxylic acid chlorides. Preferably carboxylic acid esters corresponding to the formula (I) or (II)
R1xe2x80x94C(O)xe2x80x94OR2xe2x80x83xe2x80x83(I)
R1xe2x80x94C(O)xe2x80x94CH2xe2x80x94C(O)xe2x80x94OR2xe2x80x83xe2x80x83(II)
are prepared, wherein R1 is C1-C4 alkyl or C1-C4 alkyl substituted by at least 1 halogen atom, and R2 is C1-C4 alkyl, C1-C4 alkyl substituted by at least 1 halogen atom, aryl or benzyl. R1 may also be aryl, e.g. phenyl. Particularly preferably, R1 is methyl, ethyl or methyl or ethyl substituted by at least 1 halogen atom.
Particularly preferably, C1-C4-alcohols and acid chlorides of halogenated acetic acids or halogenated acetylacetic acids are esterified. Very particularly preferably, corresponding alkyl esters of chloro-, dichloro-, trichloro-, trifluoro-, difluoro- or chlorodifluoroacetic acid are prepared, or corresponding alkyl esters of tri-, difluoro- or chlorodifluoroacetylacetic acid, in particular of trifluoroacetylacetic acid.
The invention can be performed in two variants. In the first variant, the xe2x80x9coniumxe2x80x9d salts of two special amines, DBN or DBU, are used. In this case, no additional acid is used. In the second variant, the reaction is performed in the presence of free carboxylic acid. In this variant, any nitrogen-based xe2x80x9coniumxe2x80x9d salts can be used, including DBN and DBU. The second variant will be explained in greater detail first.
According to one variant, the esterification is performed in the presence of an xe2x80x9coniumxe2x80x9d salt of the corresponding acid (preferably of a halogenated acetic acid or of the halogenated acetylacetic acid) and additionally of the corresponding (free) acid (preferably of a halogenated acetic acid or of (free) halogenated acetylacetic acid). Accordingly, both a corresponding xe2x80x9coniumxe2x80x9d salt and the free acid are present in the mixture. It is assumed that a portion of the corresponding halogenated acid can be replaced by another carboxylic acid or mineral acid. However, it is preferred if the acid chloride and the acid used to form the xe2x80x9coniumxe2x80x9d salt are the same. The molar ratio of xe2x80x9coniumxe2x80x9d salt to (free) carboxylic acid is advantageously between 1:0.2 and 1:3. Good results are for example also achieved with a ratio between 1:0.2 and 1:2. The concentration of xe2x80x9coniumxe2x80x9d salt is advantageously 5 to 20 mole % of the reactants (calculated without solvent). The presence of the free carboxylic acid can be brought about by adding it to the reaction mixture. It can also be produced in situ by adding water to the reaction mixture, because the acid chloride and water react to form the corresponding free carboxylic acid. The process can be performed continuously.
The term xe2x80x9coniumxe2x80x9d in this variant indicates cations having a positively-charged nitrogen, for example protonated aromatic nitrogen bases such as pyridinium or protonated alkyl-, dialkyl- or trialkylammonium cations, or ammonium compounds substituted by cycloalkyl, or cycloaliphatic nitrogen bases such as piperidinium or quaternary ammonium cations.
Especially suitable carboxylic acid salts are xe2x80x9cOniumxe2x80x9d salts in which xe2x80x9coniumxe2x80x9d identifies a cation of nitrogen having the formula Rxe2x80x2Rxe2x80x3Rxe2x80x2xe2x80x3Rxe2x80x3xe2x80x3N+ wherein Rxe2x80x2,Rxe2x80x3,Rxe2x80x2xe2x80x3 and Rxe2x80x3xe2x80x3, independently of each other, represent hydrogen, alkyl with 1 to 20 carbon atoms, aryl or aralkyl. Rxe2x80x2 and Rxe2x80x3 or Rxe2x80x2xe2x80x3 and Rxe2x80x3xe2x80x3, or Rxe2x80x2, Rxe2x80x2 and Rxe2x80x2xe2x80x3 or Rxe2x80x2, Rxe2x80x3, Rxe2x80x2xe2x80x3 and Rxe2x80x3xe2x80x3 may also, optionally with inclusion of the nitrogen atom, form saturated or unsaturated ring systems. xe2x80x9cArylxe2x80x9d here stands in particular for phenyl or for phenyl substituted by 1 or more C1-C2 alkyl groups. Particularly advantageous salts are those in which xe2x80x9coniumxe2x80x9d is ammonium, pyridinium or R1xe2x80x2R2xe2x80x2R3xe2x80x2R4xe2x80x2N+, wherein R1xe2x80x2, R2xe2x80x2, R3xe2x80x2 and R4xe2x80x2, independently of each other, represent hydrogen, alkyl with 1 to 15 carbon atoms, phenyl or benzyl. Examples of such cations include pyridinium, piperidinium, N-methylpiperidinium, anilinium, benzyltriethylammonium and triethylammonium.
Amines substituted by hydroxy groups, particularly cycloaliphatic amines, in particular hydroxy-substituted piperidines and N- C1-C4 alkylpiperidines, can also be used. Suitable examples include piperidines substituted at the C4 atom such as 4-hydroxypiperidine, N-methyl-4-hydroxypiperidine, N-ethyl-4-hydroxypiperidine and N-propyl-4-hydroxypiperidine.
Cations of amines which are disclosed in German Offenlegungsschrift no. DE 101 04 663.4, which does not constitute a prior publication, can also be used. These are xe2x80x9coniumxe2x80x9d cations based on a mono-or bicyclic compound with at least two nitrogen atoms, wherein at least one nitrogen atom is incorporated in the ring system. Thus xe2x80x9coniumxe2x80x9d cations based on monocyclic compounds may be used. These are then saturated or unsaturated 5-member ring, 6-member ring or 7-member ring compounds. At least one nitrogen atom is incorporated in the ring. A further nitrogen atom may also be incorporated in the ring system. Alternatively or additionally, the ring may be substituted by one or more amino groups. Dialkylamino groups in which the alkyl groups may be identical or different and comprise 1 to 4 carbon atoms are preferred. The amino group may also represent a saturated ring system, for example a piperidino group. Representatives of monocyclic ring systems which can be used effectively include dialkylaminopyridine, dialkylaminopiperidine and dialkylaminopiperazine.
xe2x80x9cOniumxe2x80x9d cations of bicyclic compounds may also be used. Here too, one, two or more nitrogen atoms may be integrated in the ring system. The compounds may be substituted by one or more amino groups. Dialkylamino groups in which the alkyl groups may be identical or different and comprise 1 to 4 carbon atoms or together with the nitrogen atom form a saturated ring system, such as for example the piperidinyl group, are again preferred.
It should be apparent from the foregoing that in this embodiment at least two nitrogen atoms in the usable compounds must have basic properties and, depending on the type of bonds, are bonded to 2 or 3 carbon atoms.
xe2x80x9cOniumxe2x80x9d salts of carboxylic acid with bicyclic amidines, in particular 1,5-diazabicyclo[4.3.0]-non-2-ene (DBN) and 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU) are very particularly preferred. These salts can also be used together with free carboxylic acid, as is possible with the xe2x80x9coniumxe2x80x9d salts described generally above.
Another variant of the invention provides for operation to be in the presence of the adduct (xe2x80x9coniumxe2x80x9d salt) of the corresponding carboxylic acid and 1,5-diazabicyclo-[4.3.0]-non-2-ene or 1,8-diazabicyclo-[5.4.0]-undec-7-ene. In this variant, the process is carried out without the presence of additional free acid.
The above xe2x80x9coniumxe2x80x9d compounds can be prepared in advance, by reacting the amines with the respective acid.
The temperature at which the reaction is carried out in the process of the invention may range from ambient temperature (approximately 20xc2x0 C.) up to the boiling point of the mixture, for example up to 100xc2x0 C. The process may be carried out at ambient pressure (approximately 1 bar absolute) or if desired also at elevated pressure, for example at a pressure of up to 5 bar absolute.
The process may be carried out either batchwise or continuously. The resulting reaction mixture may be worked-up by, for example, distillation in order to recover the product esters.
In one preferred embodiment, the formation of two phases is utilized to recover the product. This may be effected, for example, by cooling the reaction mixture to low temperatures. One phase is represented by the ester phase, which often is already highly pure.
With other esters, phase separation already occurs at ambient temperature. This applies, for example, to the methyl and ethyl esters of trifluoroacetic acid or chlorodifluoroacetic acid disclosed in co-pending U.S. patent application Ser. No. 09/113,547, filed Jul. 10, 1998 (=DE 197 32 031). Advantageously, a molar ratio of alcohol to acid chloride, as described in the aforementioned German patent specification, is set in the range of 1.01:1 to 5:1. Preferably the molar ratio of methanol to trifluoroacetyl chloride is about 1.03:1 to 4:1, the molar ratio of ethanol to trifluoroacetyl chloride is about 1.01:1 to 5:1, the molar ratio of methanol to chlorodifluoroacetyl chloride is about 1.06:1 to 2.5:1 and the molar ratio of ethanol to chlorodifluoroacetyl chloride is about 1.02:1 to 2.5:1.
In the ester production process of the invention, HCl is released when using acid chlorides. The released HCl can react with alcohol to form an alkyl chloride. It has been found that alkyl chloride formation can be largely suppressed if non-aromatic xe2x80x9coniumxe2x80x9d salts are used, in particular trialkylammonium compounds. Advantageously the suppression of alkyl chloride formation is also successful, in particular with a continuous process and removal of a two-phase mixture from the bottom of the reactor, by feeding back the catalyst phase which has been separated (which contains xe2x80x9coniumxe2x80x9d carboxylic acid salt) into those components of the reactor in which alcohol and HCl are in contact with each other, for example in the stripper or those components in which evaporating constituents of the reaction mixture are condensed under reflux.
The invention also relates to novel xe2x80x9coniumxe2x80x9d salts which can be used as a catalyst in the esterification process according to the invention. These are salts which are formed of carboxylic acid anions and xe2x80x9coniumxe2x80x9d cations based on a mono- or bicyclic compound with at least two nitrogen atoms, in which at least one nitrogen atom is incorporated in the ring system. The preferred carboxylic acid anions are those which correspond to the aforedescribed carboxylic acid esters of formula (I) or (II). Particularly preferred are carboxylic acid anions which correspond to the carboxylic acid esters described further above as being preferred. Usable and preferred xe2x80x9coniumxe2x80x9d cations are listed above. Particularly preferred are xe2x80x9coniumxe2x80x9d salts formed from dialkylaminopyridinium, dialkylaminopiperidinium or dialkylaminopiperazinium cations, the aforementioned hydroxysubstituted piperidinium cations or protonated cations of DBN and DBU as cations and trifluoroacetate, difluoroacetate, chlorodifluoroacetate, trifluoroacetylacetate, chlorodifluoroacetylacetate and difluoroacetylacetate. Salts formed from protonated cations of DBN and DBU and trifluoroacetate are very particularly preferred. The aforementioned salts may be used as a catalyst in the process of the invention.
The invention additionally relates to mixtures which comprise carboxylic acids and nitrogen-based salts of xe2x80x9coniumxe2x80x9d cations and carboxylic acid anions corresponding to the carboxylic acid in the mixture. The molar ratio of xe2x80x9coniumxe2x80x9d salt to carboxylic acid lies in the range from 1:0.2 to 1:3. Preferred xe2x80x9coniumxe2x80x9d cations (be it with one or with at least two nitrogen atoms) are described above. Preferred carboxylic acid anions are likewise described above. The mixtures according to the invention of xe2x80x9coniumxe2x80x9d salts and carboxylic acid are likewise usable as catalysts in the esterification process according to the invention. The advantage of the process according to the invention is better handling, since the precipitation of solids is avoided, and the possibility of decreasing the formation of by-products, in particular reduced alkyl chloride formation when using carboxylic acid chlorides in the esterification.